Writing in the journal Nutrition Research, researchers at Monash University Malaysia and the Malaysian Palm Oil Board showed that even supplementation with low-dose TRF (a vitamin E fraction known as tocotrienol-rich fraction) could demonstrate effective immune enhancement, augmenting IgG and IFN-γ responses.
IgG and IFN-γ are key drivers in humoral and cellular immune responses, respectively.
“These findings have significant translational potential, particularly for cost-effective public health strategies aimed at improving vaccine efficacy in healthy populations,” the researchers wrote.
This research was funded by a grant from the Malaysian Palm Oil Board, Monash University Malaysia and ExcelVite Sdn Bhd (Malaysia).
Immune enhancing potential
The immune system determines whether an individual is susceptible to infections and if they can maintain good health. Adequate nutrition plays a key role in influencing immune response.
The COVID-19 pandemic spurred interest in the immune system, preventative nutrition and nutraceuticals as more studies showed links between “higher intake of specific micronutrients and enhanced immune function,” the researchers explained. They also noted that vitamin E emerged as a potent lipid-soluble antioxidant with anti-inflammatory and antioxidative effects.
Palm oil has a vitamin E fraction called tocotrienol-rich fraction (TRF) and high concentrations of TRF are in natural sources, including oil palm pulp (Elaeis guineensis), annatto bean seeds (Bixa orellana) and rice bran (Kouchi akamai). More research shows that tocotrienols modulate key immune, metabolic, cell proliferation, lipid profile and cell signaling pathways. They offer anticancer, neuroprotective, antidiabetic and cardio protective effects. The researchers suggest TRFs could be a next-generation supplement, though they remain understudied.
The researchers noted that studies exist showing that “daily supplementation of TRF enhanced T-cell proliferation and improved both cellular and humoral immune responses and also upregulated immune-related proteins.” TRF may have immune-boosting potential, they added.
However, no studies have shown the effect of lower doses of TRF on modulating host immune system. The current study employs the influenza vaccine to gauge the immunomodulatory effect in healthy people supplemented with TRF dosages. The researchers hypothesized that daily low-dose TRF supplementation could boost immune response to the influenza vaccine in healthy participants.
Study details
The eight-week, single-center, double-blinded, randomized, placebo-controlled trial assessed the effect of TRF dosages (placebo, 50, 100, 200, and 400 mg) on immune responses following an immune challenge in 127 healthy participants between 18 to 60 years old. The study was conducted at Monash University Research Center, Thomson Hospital, Kota Damansara, Malaysia, between April 2023 and November 2024.
Participants consumed TRF capsules daily and attended three clinic visits over the study period where blood samples were collected. On day 28, pre-vaccination blood samples were gathered, followed by intramuscular administration of the influenza vaccine (Vaxigrip Tetra season 2022/2023, Sanofi Malaysia). The researchers conducted endpoint clinical data and health screening at trial completion.
“While all participants mounted strong antibody responses by day 56 against influenza antigens, the TRF-supplemented groups showed a significantly higher IgG titer compared to placebo at the study endpoint, with no significant differences observed between the TRF-supplemented groups,” the researchers wrote. “Notably, 400 mg group exhibited the highest total antibody titers compared to the lower doses on day 56.”
More studies are needed on long-term TRF supplementation to determine whether it could lead to sustained higher antibody titers and longer-lasting immunological memory, the scientists explained. This could offer clinical insights for vaccine booster scheduling and the use of TRF as an adjuvant with other vaccine platforms, including mRNA (COVID-19), viral vector (e.g., adenovirus-based), and protein-subunit vaccines (e.g., hepatitis B, HPV).
The researchers also suggest future studies may explore different TRF interactions, including with the gut microbiome, “given that immune responses are profoundly influenced by gut-associated lymphoid tissue and TRF may alter gut microbial composition.”
Source: Nutrition Research. doi: 10.1016/j.nutres.2026.07.004. “Immunomodulatory effects of palm-derived tocotrienol-rich fraction in healthy volunteers following influenza vaccination: A randomized clinical trial”. Authors: Shuyu Chen et al.
